List of ContributorsPrefaceContents of Previous VolumesSection 1. Cell Differentiation and Interaction Cell Division in the Normal Central Nervous System I. Introduction II. Neural Epithelium. Ventricular and Subventricular Layers III. Mitotic Cells of Ectodermal Origin IV. Mitotic Cells of Mesodermal Origin V. Conclusions References Schwann Cells: an In Vitro Perspective I. Introduction II. In Vitro Systems III. Control ofSchwann Cell Proliferation IV. Myelin-Related Behaviors In Vitro V. Schwann Cell Influences Directed to Neurons VI. Conclusions and Projections References Molecular and Cell Biological Aspects of Learning: Toward a Theory of Memory I. Introduction II. Studies of Biochemical Correlates of Learning III. Neurochemical Behavioral Modulating Factors IV. Long-Term Potentiation as a Model System for Learning V. Studies of Neuroanatomical Changes VI. Current Status and Theoretical Concepts ReferencesSection 2. Aging and Pathology Immunocytochemical Studies of Astrocytes in Normal Development and Disease I. Introduction II. The GlialFibrillary Acidic Protein III. Relation ofGlial Filaments to Neurofilaments and Microtubules IV. Function of GFA Protein V. Functions of GFA Protein-Containing Cells VI. GFA Protein Immunocytochemistry and Retrospective Pathology References Aging of Autonomic Synapses I. Aging of Autonomie Synapses: Some Basic Questions II. Aging of Autonomie Neurons: A Background III. Age-Dependent Modifications of Axonal Transport IV. The Chicken as an Animal Model of Aging V. Acetylcholine Metabolism in Aging Avian Synapses VI. Catecholamine Metabolism in Aging Avian Synapses VII. Aging of Noradrenergic Neurons: A Comparison of CNS and PNS VIII. Common Characteristics of Cholinergic and Adrenergic Terminals during Aging IX. Variations in Cholinergic Receptors with Aging. CNS versus PNS X. Development and Aging of Synapses: A Single Process? XI. Conclusions: Toward a Pharmacology of Aging Synapses References Axonal Elongation in Peripheral and Central Nervous System Transplants I. Introduction II. Regeneration in the Peripheral and Central Nervous Systems III. Transplants of Nonneuronal Cells IV. Transplantation of Neurons and Target Tissues V. Discussion References Demyelination I. Introduction II. Myelin III. Animal Models of Immunologically Mediated Demyelination IV. Tissue Culture Studies of Demyelination V. Conclusions References CNS Hypomyelinated Mutant Mice: Morphological and Tissue Culture Studies I. Introduction II. Historical Background III. The Common Clinical Syndrome IV. Genetics and Morphology of Specific Mutations V. Experimental Analysis: The Tissue Culture System ReferencesSection 3. Methodologies Progress in Cerebral Micro-vascular Studies Related to the Function of the Blood-Brain Barrier I. Introduction II. Endothelial Cell Cultures III. CerebralMicrovessels IV. Conclusions References Isolation and Characterization of the Cells of the Cerebral Microvessels I. Introduction II. Isolation of Microvessels III. Culture of Vessels and Derived Cells IV. Studies on Cells Derived from Microvessels V. Concluding Remarks References PCI2 Pheochromocytoma Cultures in Neurobiological Research I. Introduction II. Historical Background III. The Classification of PC12 Cells IV.
Schwann Cells: An in Vitro Perspective
Silvio Varon and Marston Manthorpe, Department of Biology and School of Medicine, University of California, San Diego, La Jolla, California
Publisher Summary
This chapter provides a detailed survey of the in vitro tools that have become available for the investigation of Schwann cells. Satellite and Schwann cells spend most of their developmental life in close physical contact with the neuron. This topographical feature has been examined in great detail using histological and ultrastructural techniques and has prompted a firm belief that biochemical and functional interactions must parallel the physical associations. The most conspicuous Schwann–neuron interaction is the generation of myelin around certain axons; the formation, maintenance, breakdown, and restoration of myelin have been extensively investigated in vivo. The complex relationship between Schwann cells and the neuronal membrane strongly implies that these other roles are of critical importance to normal peripheral nervous system (PNS) function. This chapter discusses the main points derived from the in vivo studies of normal and pathological situations. The chapter presents the review of several culture systems that permit an analysis of (1) Schwann cell properties and their modulation under different culture environments and (2) Schwann cell–neurite interactions and the consequences resulting from them for both glial and neuronal partners.
I Introduction
A Glial Cells in the Peripheral Nervous System
B Normal Development of Schwann Cells in Vivo
C Pathological Developments in Vivo
II In Vitro Systems
A Culture Methods
B Identification Criteria
III Control of Schwann Cell Proliferation
A Rat Schwann Cells: Neuritic Mitogens
B Rat Schwann Cells: Soluble Mitogens
C Chick Embryo Schwann Cells: Soluble Mitogens
D Mouse Schwann Cells: Serum and Other Mitogens
E Schwann Cell Proliferation in Vivo and in Vitro
IV Myelin-Related Behaviors in Vitro
A Physical Associations between Schwann Cells and Neurites
B Schwann Cell Production of Basal Lamina and Collagens
C Myelin-Related Markers
D Peripheral Neurites and Central Myelin
V Schwann Cell Influences Directed to Neurons
A Neuronotrophic Factors of Schwann Cell Origin
B Neurite-Promoting Factors of Schwann Cell Origin
VI Conclusions and Projections
References
I Introduction
A Glial Cells in the Peripheral Nervous System
In the peripheral nervous system (PNS), glial cells occur in two categories: (i) the satellite cells that surround the neuronal somata within the ganglionic mass, and (ii) the Schwann cells that surround the axons coursing outside the central nervous system (CNS), whether such axons derive from PNS ganglionic neurons or CNS spinal cord motor ones and whether or not they become myelinated. As shall be pointed out throughout this review, these two subdivisions of peripheral glia are likely to represent the same cell element assuming different morphological, biochemical, and possibly functional properties according to their position relative to the neuron. The term “Schwann cell,” which will be generally used in the review, therefore may well include the satellite subset of peripheral glial cells.
Satellite and Schwann cells spend most of their developmental life in close physical contact with the neuron. This topographical feature has been examined in great detail using histological and ultrastructural techniques and has prompted a firm belief that biochemical and functional interactions must parallel the physical associations. The most conspicuous Schwann-neuron interaction is the generation of myelin around certain axons; formation, maintenance, breakdown, and restoration of myelin have been extensively investigated in vivo. Much less attention, however, has been given to the identification and characterization of other roles that Schwann cells must play. The complex relationship between Schwann cells and the neuronal membrane strongly implies that these other roles are of critical importance to normal PNS function. Glia-neuron interactions in the CNS are equally indicative of similar glial roles (cf. Varon and Somjen, 1979).
Schwann-neuron interactions must be considered to occur in two ways, from neuron to glia and from glia to neuron. Communications in either direction are likely to be mediated by both macrosignals (i.e., macromolecules presented on cell surface membranes or transmitted through the intercellular fluid) and microsignals (ions, neurotransmitter-related molecules, metabolites, etc.). In vivo studies have provided evidence for the occurrence of some such signals. We know that neurites supply Schwann cells with mitogenic and myelinogenic signals, triggering proliferation and myelin-forming processes, respectively (Asbury, 1967; Landan and Hall, 1976; Speidel, 1964; Friede and Samorajski, 1968; Raine, 1977). Certain transmitters, such as γ-amino butyric acid (GABA), have been shown to be avidly taken up by satellite cells (Schon and Kelly, 1974a,b; Bowery et al., 1979a,b), even though the functional meaning of this glial property remains unclear. There is a strong suspicion that Schwann cells provide signals for both growth and guidance of regenerating axons (cf. Varon and Bunge, 1978; Varon and Somjen, 1979). Nevertheless, thus far, in vivo studies have failed to characterize in any detail the signals themselves and/or their immediate responses.
In recent years a new, very powerful tool has been developed, namely the use of neural cell cultures (cf. Varon, 1975b; Fedoroff and Hertz, 1978; Schoffeniels et al., 1978; Giacobini et al., 1980). In vitro studies can strongly complement in vivo ones. Under appropriate culture circumstances, both neurons and glial cells can display the typical features and behaviors for which they are known in vivo, and thus “recapitulate” development or regeneration as they are perceived in situ (Waxman et al., 1977). In addition, they offer opportunities not available to in vivo research, such as (i) purified populations of Schwann cells and neurons, which can be investigated separately from or after controlled recombination with each other, and (ii) living cells that can be examined in an environment that is uniform, controlled, and amenable to experimental modification.
This review will attempt to provide a detailed survey of the in vitro tools that have become available for the investigation of Schwann cells, and of the substantial amount of information already accumulated through their use. As a background to the following sections, the remainder of this first section will summarize main points derived from in vivo studies of normal and pathological situations. For a detailed coverage of in vivo studies, the reader is encouraged to consult some of the several reviews already available on the subject (Bunge, 1970; Webster, 1974; Aguayo et al., 1979; Pannese, 1980; among others).
B Normal Development of Schwann Cells in Vivo
1 Origin and Migration
The development of trunk neural crest has been a favorite object of investigation, thanks to the possibility of placing into a chick embryo homotypic or heterotypic grafts of “marker” neural crest cells ([3H]thymidinelabeled chick embryo cells, or quail cells identifiable by their special nuclear features) and following the subsequent fate of the marker cells. In this manner, various investigators have reported that the majority of Schwann cells (or their precursors) migrate from their origin in the neural crest to their final neuronal residence (Weston, 1963, 1970; Johnston, 1966; Johnston et al., 1974; Noden, 1975;...
